Can we prevent stent restenosis after coronary stent implantation Can we prevent stent restenosis after coronary stent implantation? Benefits of trimetazidine on the incidence of stent restenosis after percutaneous coronary intervention. Chen J et al. Int J Cardiol. 2014;173(3):597-600.

Preventive effect of trimetazidine on post-PCI restenosis INTRODUCTION In previous studies, pretreatment with trimetazidine has been shown to prevent myocardial injury during percutaneous coronary intervention.1 Trimetazidine has also been shown to reduce recurrent angina, and to preserve left ventricular function after PCI.2 Despite successful PCI, and despite the introduction of a drug-eluting stent (DES), patients are still highly prone to restenosis.3 The present study investigates whether trimetazidine could also have a beneficial effect on the occurrence and progression of stent restenosis. 1. Bonello L et al. Heart. 2007;93:703-707. 2. Xu X et al. Clin Drug Investig 2014;34:251–258. 3. Chen J et al. Int J Cardiol. (2014) 2014;173(3):597-600.

Preventive effect of trimetazidine on post-PCI restenosis METHODOLOGY 768 patients undergoing PCI for the first time randomized into the trimetazidine group (n=384) and control group (n=384). After DES implantation, all patients were treated with regular medication. In the trimetazidine group, trimetazidine was administrated at 20 mg tid* for at least 30 days. All patients received blinded follow-up angiography 9 to 13 months after discharge. Primary end point: Restenosis Secondary end point: Major adverse cardiac and cerebrovascular events (MACCEs). 768 patients were enrolled and randomized into the trimetazidine group (n=384) and control group (n=384). After DES implantation, all patients were treated with regular medication including double antiplatelet therapy (aspirin at 100 mg/day, indefinitely, and clopidogrel was administered at 75 mg/day for at least 1 year), statins of different doses indefinitely, and other drugs if necessary. In the trimetazidine group, trimetazidine was administrated at 20 mg tid for at least 30 days. All patients received follow-up angiography 9 to 13 months after discharge. Angiographic restenosis was defined as 50% or more luminal narrowing in the target lesion. Major adverse cardiac and cerebrovascular events (MACCEs) were recorded. Chen J et al. Int J Cardiol. 2014;173(3):597-600. *Trimetazidine 20 mg tid is equivalent to trimetazidine 35 mg bid.

Preventive effect of trimetazidine on post-PCI restenosis RESULTS Results on restenosis The trimetazidine group has a lower incidence of stent restenosis compared with the control group (4.2% vs 11.1%; P=0.001). % of events P=0.001 11.1 This result suggests that trimetazidine treatment reduced stent restenosis by 62.2%, compared with control. 4.2 Chen J et al. Int J Cardiol. 2014;173(3):597-600.

Preventive effect of trimetazidine on post-PCI restenosis RESULTS Results on restenosis and the number of MACCEs The incidence of MACCEs is also significantly decreased in the trimetazidine treatment group at the 1-year follow-up visit (6.1% vs 10.8%; P=0.034). This result suggests that trimetazidine treatment reduced the number of MACCEs by 43.5% compared with no treatment. MACCEs include: death from any cause, nonfatal myocardial infarction, revascularization stroke, and cerebral bleeding. Chen J et al. Int J Cardiol. 2014;173(3):597-600.

Preventive effect of trimetazidine on post-PCI restenosis RESULTS Results on predictors for stent restenosis Several predictors for stent restenosis have been identified. Among these predictors, diabetes mellitus, current smoking, stent diameter and length, and age have been shown to stimulate restenosis, while trimetazidine has been shown to prevent restenosis. This study also identified several predictors for stent restenosis after PCI at the 1-year follow-up exam. Trimetazidine treatment has been shown to be a predictor of protection against stent restenosis after PCI. Similar to the results of other studies, we found that age, diabetes mellitus, current smoking, mean stent length, and mean stent diameter were also associated with stent restenosis. Trimetazidine: a predictor of protection Chen J et al. Int J Cardiol. 2014;173(3):597-600.

Preventive effect of trimetazidine on post-PCI restenosis CONCLUSION Even after successful PCI with DES, patients need to be better protected against restenosis. Trimetazidine seems to be protective against stent restenosis in angina patients who undergo PCI. Trimetazidine also may effectively prevent the occurrence of MACCEs. Myocardial injury prevention during PCI and reduction of post-PCI angina symptoms persistence have been observed with trimetazidine All these results suggest that trimetazidine should be combined early in the management of ischemic patients to protect their heart, especially when they undergo PCI. According to the authors, trimetazidine treatment could also improve endothelial dysfunction and preserve heart function after stent implantation. This could explain the results of this study. It is well known that vascular endothelial cells normally provide an efficient barrier against thrombosis, lipid uptake, and inflammation, and the endothelium is critical in the pathology of atherosclerosis and stent restenosis. In recent years, more and more studies have found that, in some patients, stent restenosis is not the result of proliferation and migration of smooth muscle cells, but rather the result of in-stent neoatherosclerosis due to the delay of re-endothelialization at the area of the stent. Therefore, drugs with the ability to protect the endothelium or accelerate endothelial recovery would be helpful to post-PCI patients. Thus, it seems that the effect of trimetazidine on the endothelium could contribute greatly to its role in the inhibition of stent restenosis observed in our study. Chen J et al. Int J Cardiol. 2014;173(3):597-600.